Causes of Hepatocellular Carcinoma
Hepatitis B, hepatitis C, and diabetes mellitus are established causes of hepatocellular carcinoma, while chronic renal failure and chronic respiratory failure are not recognized risk factors for HCC.
Established Viral Causes
Hepatitis B and hepatitis C are the most important causes of HCC globally, accounting for approximately 78% of hepatocellular carcinoma cases and representing the leading etiologic factors worldwide 1.
- Hepatitis B virus increases the risk of HCC by 1000-fold in the setting of cirrhosis and is the major cause of cirrhosis and HCC in Asia and Africa 1
- Hepatitis C virus is the most common underlying liver disease among patients with cirrhosis in North America, Europe, and Japan, with 1-2% per year developing HCC once cirrhosis is established 1
- Chronic HBV infection carries a 15-25% risk of premature death from liver cancer or end-stage liver disease 2
Diabetes Mellitus as a Risk Factor
Diabetes mellitus is an established risk factor for HCC, particularly through its association with metabolic dysfunction-associated steatotic liver disease (MASLD/NAFLD) 1.
- The combination of insulin resistance, hypertension, dyslipidemia, and obesity (metabolic syndrome) has been recognized as a cause of nonalcoholic fatty liver disease, cirrhosis, and hepatocellular carcinoma 2
- Diabetic patients are at risk for HCC as a result of hepatic injury, fibrosis, and eventual cirrhosis resulting from fatty liver disease 3
- MASLD affects up to 19% of adults in Western nations and contributes 10-14% of cirrhosis cases, with an 18-27% risk of developing cirrhosis 2
Important Caveat on Diabetes
- Diabetes alone without concomitant viral hepatitis or liver disease may not be sufficient to increase HCC risk 4
- The risk becomes clinically significant when diabetes occurs in the context of metabolic syndrome and progressive liver disease 5, 3
Non-Risk Factors
Chronic renal failure and chronic respiratory failure are not recognized causes or risk factors for hepatocellular carcinoma in any of the major international guidelines or research literature 1.
- These conditions do not appear in diagnostic work-up algorithms for HCC risk assessment 1
- No mechanistic pathway links these organ failures to hepatocellular carcinogenesis 6, 7
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